Development of olmesartan medoxomil lipid-based nanoparticles and nanosuspension: preparation, characterization and comparative pharmacokinetic evaluation

Figures & data

Table 1. Composition of olmesartan medoxomil-loaded SLNs, nanosuspension and coarse suspension.

	Formulation code for SLNs
Ingredients (mg)	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	CS	NS
OM	10	10	10	10	10	10	10	10	10	10	10	400
Dynasan-118	100	–	–	–	200	–	–	–	–	–	–	–
Stearic acid	–	–	100		–	200	–	–	–	–	–	–
Stearyl amine	–	100	–	200	–	–	–	–	–	–	–	–
GMS	–	–	–	–	–	–	100	–	–	–	–	–
GMS + SA (1:1)^a	–	–	–	–	–	–	–	56.6 + 44.4	–	–	–	–
GMS + SA (1:0.5)^a	–	–	–	–	–	–	–	–	77.9 + 22.1	–	–	–
GMS + SA (1:0.1)^a										95.6 + 4.4	–	–
PVPk30	–	–	–	–	–	–	–	–	–	–	–	1.01%
Tween 80	–	–	–	–	–	–	–	–	–	–	–	1.05%
Egg lecithin	100	100	100	100	100	100	100	100	100	100	–	–
Chloroform:methanol (1:1) (mL)	10	10	10	10	10	10	10	10	10	10		–
Aqueous phase
Na CMC	–	–	–	–	–	–	–	–	–	–	50	–
Poloxamer-188 (mg)	150	150	150	150	150	150	150	150	150	150	–	–
Double-distilled water (mL)	10	10	10	10	10	10	10	10	10	10	10	20

CS: coarse suspension; NS: nanosuspension.

^a Molar ratios are taken.

Table 2. Physical characters – size, PDI, EE and content of OM-SLNs and nanosuspension (mean ± SD, n = 3).

Parameter	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	NS
Size (nm)	82.8 ± 2.9	106.1 ± 7.3	194.1 ± 14.3	247.2 ± 8.5	138.3 ± 4.5	242.9 ± 8.2	170.9 ± 2.1	369.9 ± 11.3	128.7 ± 5.1	122.7 ± 10.8	573.5 ± 38.2
PDI	0.176 ± 0.13	0.208 ± 0.01	0.267 ± 0.1	0.494 ± 0.07	0.27 ± 0.03	0.396 ± 0.04	0.469 ± 0.05	0.75 ± 0.07	0.563 ± 0.1	0.369 ± 0.02	0.308 ± 0.05
ZP (mV)	–14.92 ± 0.9	+6.3 ± 0.6	–17.6 ± 1.5	+33.7 ± 0.7	–18.3 ± 0.6	–11.5 ± 1.3	–8.13 ± 0.37	–20.6 ± 0.2	–28.2 ± 4.6	–28.3 ± 1.9	–25.7 ± 2.3
Assay (mg)	9.98 ± 1.54	9.54 ± 1.04	9.73 ± 0.64	9.51 ± 0.71	9.81 ± 0.51	9.62 ± 0.41	9.50 ± 1.21	9.36 ± 0.89	9.80 ± 0.81	9.71 ± 0.11	9.90 ± 0.18
EE (%)	90.4 ± 0.39	79.81 ± 0.59	82.79 ± 1.52	81.7 ± 0.15	94.2 ± 0.61	86.17 ± 0.32	87.0 ± 0.91	77.4 ± 0.61	80.9 ± 0.51	84.3 ± 1.34	NA

Figure 1. (A) In vitro release of OM-SLNs in 0.1 N HCl followed by pH 6.8 phosphate buffer (mean ± SD, n = 3). (B) Dissolution profile of OM-NS (mean ± SD, n = 3).

Table 3. Physical stability studies of the optimized formulation (F10) at room temperature (25 °C) and refrigerated temperature (4 °C) (mean ± SD, n = 3).

	At room temperature				At refrigerated temperature
Day	Size (nm)	PDI	ZP (mV)	EE (%)	Size (nm)	PDI	ZP (mV)	EE (%)
1	122.7 ± 10.8	0.369 ± 0.02	28.3 ± 1.90	84.3 ± 1.34	122.7 ± 10.8	0.369 ± 0.02	28.3 ± 1.9	84.3 ± 1.34
15	138 ± 5.54	0.388 ± 0.09	27.63 ± 1.8	82.36 ± 0.41	132.6 ± 4.7	0.360 ± 0.01	27.9 ± 1.1	83.56 ± 0.92
30	165.76 ± 5.58	0.405 ± 0.08	26.6 ± 2.26	80.46 ± 0.45	153.5 ± 9.2	0.387 ± 0.07	26.83 ± 1.2	82.66 ± 0.58
60	188.76 ± 7.52	0.417 ± 0.06	25.6 ± 1.90	79.76 ± 0.75	173.8 ± 5.6	0.403 ± 0.05	26.23 ± 1.2	81.4 ± 0.65

Figure 4. SEM photographs of (a) dynasan118 SLNs (at magnification ×30k) (F1) and, (b) GMS-SA SLNs (at magnification ×15k) (F10).

Figure 5. Mean serum concentration versus time profiles of OM coarse suspension, nanosuspension, solid lipid nanoparticles upon oral administration to male albino Wistar rats (mean ± SD, n = 6).

Table 4. PK Parameters of optimized OM nanosuspension, SLNs formulation (F10) and coarse suspension (mean ± SD., n = 6).

Parameter	SLN (F10)	NS	Control suspension
Cmax (μg/mL)	5.17 ± 0.45*	5.08 ± 0.50#	1.76 ± 0.16
tmax (h)	4.00*,$	1.33 ± 0.52$	2.00
AUCtot (μg h/mL)	77.19 ± 7.25*,$	33.6 ± 2.59#	10.68 ± 0.86
t1/2 (h)	15.51 ± 2.24*,$	5.22 ± 1.16	4.79 ± 0.58
MRT (h)	21.89 ± 2.92*,$	6.36 ± 0.62	5.96 ± 0.59

* p < .01 when SLN was compared with control.

# p < .01 when NS was compared with control.

$ p < .01 when SLN was compared with nanosuspension.